To Assess Safety/Efficacy of ELAD in Subjects w/ Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure

Severe Acute Alcoholic Hepatitis Clinical Trial

Official title:

A Randomized, Open-Label, Multicenter, Controlled Study to Assess Safety and Efficacy of ELAD® in Subjects With Severe Acute Alcoholic Hepatitis (sAAH) and Lille Score Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01829347
• Other study ID #: VTI-210
• Status: Terminated
• Phase: Phase 3
• Start date: April 2014
• Est. completion date: September 2018

Study information

• Verified date: February 2019
• Source: Vital Therapies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if treatment with the ELAD System is safe and effective in subjects with severe acute alcoholic hepatitis and Lille score failures (Lille score >0.45).

Description:

The Lille score will be used to identify subjects with an increased risk of mortality (Lille score failures). The Lille score is a prognostic model combining six reproducible variables at Day 0 and Day 7 of steroid treatment. The Lille score used in this protocol is being used independent of steroid administration during the 7 days of evaluation. A Lille score >0.45 (Lille score failure) indicates that the subject is at substantially increased risk of 30- and 90-day mortality. Subjects with severe acute alcoholic hepatitis (sAAH) are often treated with steroids as soon as their diagnosis is confirmed. This study is to assess treatment with the ELAD System in subjects who have failed per the Lille criteria, independent of steroid administration. ELAD treatment is done continuously for up to 10 days in addition to standard of care treatment. The Control group (those randomized not to receive ELAD treatment) will also get standard of care treatment. Standard of care is defined as the usual care for diet, medications, treatment of complications that may arise, etc. for sAAH patients.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: September 2018
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 ;

• Total bilirubin =8 mg/dL;

• Medical history of alcohol abuse with evidence of a causal and temporal (<6 weeks) relationship to the use of alcohol and hospital admission for this episode of sAAH;

• Maddrey score =32

• A clinical diagnosis of severe acute alcoholic hepatitis (sAAH);

• Subject must have liver biopsy or in investigator's opinion, if risk is too great to perform liver biopsy, then clinical diagnosis is sufficient;

• Subject must be a Lille score failure (Lille score >0.45) as defined in this study.

Exclusion Criteria:

• Platelet count <50,000/mm3;

• International Normalization Ratio (INR) >3.0;

• MELD score >35;

• Evidence of infection unresponsive to antibiotics;

• Evidence of jaundice for >3 months;

• Hospital admission for any episodes of liver decompensation not related to sAAH, (other than this episode of sAAH) within the past 2 months;

• Evidence of hemodynamic instability;

• Evidence of active bleeding or of major hemorrhage defined as requiring =2 units of packed red blood cells to maintain a stable hemoglobin occurring within 48 hours of Screening;

• Evidence of occlusive portal vein thrombosis impairing hepatopetal flow, or evidence of bile duct obstruction;

• Evidence by physical exam, history, or laboratory evaluation of significant concomitant disease with expected life expectancy of less than 3 months;

• Clinical evidence of liver size reduction due to cirrhosis, unless Investigator interpretation of the clinical evidence indicates liver size of <10 cm or volume of <750 cc is not considered reduced for the individual subject;

• Chronic end-stage renal disease requiring chronic hemodialysis for more than 8 weeks (not classified as hepatorenal syndrome);

• Uncontrolled seizures;

• Positive serologies for viral hepatitis B or C;

• Pregnancy as determined by ß-human chorionic gonadotropin (HCG) results;

• Participation in another investigational drug, biologic, or device study within one month of enrollment, except for observational studies (the observational study setting should not affect the safety and/or efficacy of the VTI-210 clinical trial);

• Currently listed or scheduled for liver transplant during the 90-day study period;

• Previous liver transplant;

• Previous participation in a clinical trial involving ELAD;

• Has a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or local equivalent) or any other Advanced Directive limiting Standard of Care in place (the DNR/DNI criterion is not applicable in the UK);

• Refusal to participate in the VTI-210E follow-up study;

• Is unable to provide an address for follow-up home visits.

And other inclusion/exclusion criteria

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic
• Severe Acute Alcoholic Hepatitis

Intervention

Biological:
• ELAD
ELAD is an extracorporeal system that draws blood from the subject via a dual-lumen catheter placed in a large vein, and then separates the plasma fluid (ultrafiltrate) from cellular components using a specifically-designed ultrafiltrate generator cartridge. While the cellular components are returned to the subject via the venous access, the ultrafiltrate is circulated at a high flow rate through the four metabolically-active ELAD cartridges which contain cloned, immortalized human hepatoblastoma cells (VTL C3A cells) derived from a subclone of the human hepatoblastoma cell line HepG2.

Other:
• Standard of Care treatment
Standard of care treatment is predefined treatment for sAAH complications (ascites, hepatic encephalopathy, varices, etc.) per AASLD/EASL Guidelines.

Locations

Country	Name	City	State
Germany	Charité Campus Virchow-Klinikum Medizinische Klinik	Berlin
Germany	Medizinische Hochschule Hannover	Hannover
Spain	Hospital Universitario de Cruces	Baracaldo	Vizcaya
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago de Compostela	La Coruña
Spain	Hospital Universitario de Valme	Sevilla
Spain	Hospital Universitario y Politécnico La Fe	Valencia
United Kingdom	Brighton & Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Doncaster Royal Infirmary	Doncaster	South Yorkshire
United Kingdom	NHS Tayside	Dundee	Scotland
United Kingdom	Royal Free Hospital	Hampstead	London
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	King's College Hospital NHS Foundation Trust	London	England
United States	Emory University Hospital	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Johns Hopkins University Hospital	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	North Shore University Hospital	Manhasset	New York
United States	University of Miami Hospital	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center - Twin Cities Campus	Minneapolis	Minnesota
United States	Rutgers University Hospital	Newark	New Jersey
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center, San Antonio	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	Swedish Medical Center	Seattle	Washington
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Vital Therapies, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	The primary endpoint of the study was a comparison of overall survival (OS) between ELAD-treated and Control groups, with protocol VTI-210E providing additional survival data up to a maximum of 5 years, that was included as available at the time of database lock (11 July 2016).	Up to at least Study Day 91, with protocol VTI-208E providing additional survival data at the time of database lock (11 July 2016), approximately 27 months
Secondary	Proportion of Survivors at Study Day 91.	Assess the proportion of survivors at Study Day 91.	Up to Study Day 91.

External Links

•   Sponsor's website